Comparison of the effects of sevoflurane and isoflurane on myocardial
protection in coronary bypass surgery
Koroner baypas cerrahisinde miyokardiyal korumasında sevofluran ve isofluranın etkilerinin
karşılaştırılması
Address for Correspondence/Yaz›şma Adresi: Dr. Dilek Ceyhan, Department of Anesthesiology and Reanimation, Eskişehir School of Medicine, Eskişehir Osmangazi University, Eskişehir, Turkey Phone: +90 222 239 29 79 Fax: +90 222 239 37 74 E-mail: drdcetinkaya@mynet.com
Accepted Date/Kabul Tarihi: 16.12.2010 Available Online Date/Çevrimiçi Yayın Tarihi: 05.04.2011
©Telif Hakk› 2011 AVES Yay›nc›l›k Ltd. Şti. - Makale metnine www.anakarder.com web sayfas›ndan ulaş›labilir. ©Copyright 2011 by AVES Yay›nc›l›k Ltd. - Available on-line at www.anakarder.com
doi:10.5152/akd.2011.059
Dilek Ceyhan, Belkıs Tanrıverdi, Ayten Bilir
Department of Anesthesiology and Reanimation, Faculty of Medicine, Eskişehir Osmangazi University, Eskişehir, Turkey
ÖZET
Amaç: Bu prospektif randomize çalışmanın amacı sevofluran ve isofluranın koroner baypas cerrahisi sırasında miyokart üzerindeki koruyucu etki-lerini karşılaştırmaktır.
Yöntemler: Etomidat (0.3 mg /kg ) ile genel anestezi indüksiyonunu takiben 0.1 mg/kg pankuronyum ve 1 mikrogr/kg remifentanil bolus olarak verildi. Anestezi idamesi Grup 1’deki hastalarda (n=20) %2-4 değerinde sevofluran, Grup 2’deki hastalarda (n=20) %1-2 değerinde isofluranla sağlandı. Anestezi indüksiyonundan önce, aortik klemp kaldırıldıktan sonra ve postoperatif periyotta arteriyel kan örnekleri alındı. Bu örneklerde Troponin T, kreatinin kinaz ve kreatinin kinaz MB değerleri ölçüldü. İstatistiksel analizler -iki-yönlü ANOVA ve Mann-Whitney testleri ile yapıldı.
Bulgular: Kalp hızı sevofluran grubunda pompa periyodunda, pompadan çıkış sonrası 10. ve 20. dakikalarda anlamlı yüksek bulunmuştur. CKMB düzeyi postoperatif 24. saatte sevofluran grubunda isofluran grubuna göre anlamlı düşüktür. Troponin T kros- klemp kaldırıldıktan sonra (1.015 (0.935-1.850) ng/ml, 1.469 (1.290-1.645) ng/ml, p<0.001) ve postoperatif 24.saatte (5.345±0.654 ng/ml, 8.715±1.020 ng/ml, p<0.001) sevofluran grubunda isoflu-ran grubu ile karşılaştırıldığında anlamlı düşüktür.
Sonuç: Miyokardiyal hasarlanma işaretleyicileri olan troponin T ve CKMB düzeylerinin daha düşük düzeylerde saptanması ile sevofluranın isoflu-rana göre miyokardiyal korumayı daha iyi sağlamakta olduğu kanısındayız. (Anadolu Kardiyol Derg 2011; 11: 257-62)
Anahtar kelimeler: Sevofluran, isofluran, miyokardiyal koruma, koroner baypas cerrahisi
A
BSTRACTObjective: The aim of this prospective randomized study was to compare the myocardial protective effects of sevoflurane and isoflurane during coronary bypass surgery.
Methods: After induction of general anesthesia with etomidate 0.3 mg/kg, a bolus dose of pancuronium 0.1 mg/kg and remifentanil 1 mcg/kg was administered. For the maintenance of anesthesia, patients received either sevoflurane (n=20) at 2-4% or isoflurane (n=20) at 1-2%. Arterial blood samples were obtained as follows: before induction of anesthesia, after aortic unclamping, at postoperative period. Troponin-T, creatine kinase (CK), and creatine kinase-MB (CKMB) values were measured in all obtained samples. Statistical analysis was performed using two-way ANOVA analysis and Mann-Whitney test.
Results: Heart rate was significantly higher in the sevoflurane group during the aortic side-clamp period, at the 10th minute and 20th minute after
cardiopulmonary bypass (CPB) ending. The CK-MB values at 24th postoperative hour in the sevoflurane group were found to be significantly
lower from the isoflurane group. The troponin-T values following the removal of the cross-clamp (1.015 (0.935-1.850) ng/ml vs 1.469 (1.290-1.645) ng/ml, p<0.001) and those at the 24th postoperative hour (5.345±0.654 ng/ml vs 8.715±1.020 ng/ml, p<0.001) were significantly lower in the
sevo-flurane group when compared to those in the isosevo-flurane group.
Conclusion: Sevoflurane provides a better myocardial protection than isoflurane, as may be inferred by the lower levels of the myocardial injury markers troponin-T and CK-MB observed with sevoflurane. (Anadolu Kardiyol Derg 2011; 11: 257-62)
Introduction
It is well known that coronary artery bypass graft (CABG) surgery contributes to the myocardial dysfunction, and is asso-ciated with high morbidity and mortality. The effectiveness of myocardial preservation will decrease consequences of isch-emia/reperfusion injury and duration of in-hospital stay (1). Many methods have been tried as means for myocardial protec-tion. Systemic hypothermia (with its influence on collateral flow to the heart), topical hypothermia and above all, some combina-tion of the available cardioplegic techniques are used for this purpose (2). Experimental data indicate that volatile general anesthetics have protective effects against ischemia-reperfu-sion injury that is independent of their hemodynamic effects (3). Volatile anesthetics have been shown to have a precondition-ing-like effect, resulting in protection against myocardial infarc-tion and irreversible myocardial dysfuncinfarc-tion. Volatile anesthet-ics have also been shown to provide protection against reperfu-sion injury when administered after myocardial ischemia (4, 5). However, the studies on the effects of sevoflurane and isoflu-rane on myocardial protection reported conflicting results.
The aim of this study is, to compare the myocardial protec-tive effects (by means of investigated enzyme profile) of sevoflu-rane and isoflusevoflu-rane administered to patients selected for CABG surgery during the whole time span of the surgery, including the hypothermic cardiac arrest period when sevoflurane and isoflu-rane are administered by the cardiopulmonary bypass (CPB) machine.
Methods
Patients
In this prospective randomized study, following approval by the hospital’s Ethic Committee (protocol-2005/416), our study was conducted on 40 American Society of Anesthesiologists (ASA) Class I-II patients, aged 48-69 years, scheduled for elec-tive CABG surgery. The patients were randomly allocated into two groups of 20 patients each.
Patients with a history of myocardial infarction within the past 6 months, those with ejection fraction less than 40%, those who needed valvular or aortic surgery in addition to the planned CABG surgery, unstable angina patients, emergency cases, patients with high cardiac enzymes 24 hours prior to surgery, hemodynamically unstable patients (requiring inotropic agents support or intraaortic balloon pump preoperatively), patients with any severe systemic disease, diabetes mellitus, and patients on immune-suppressive therapy were excluded from the study. None of the patients included received theophylline.
Perioperative and operative period
All patients were premedicated with morphine 0.1 mg/kg intramuscular (im) 30 minutes before the surgery. Radial arterial catheter placed under local anesthesia prior to induction. After
induction of general anesthesia with etomidate 0.3 mg/kg intra-venously (iv), a bolus dose of pancuronium 0.1 mg/kg and remi-fentanil 1 mcg/kg was administered. For the maintenance of anesthesia, group 1 (n=20) patients received volatile anesthesia with sevoflurane at 2-4% and group 2 (n=20) patients with isoflu-rane at 1-2%. Following intubation, the patients in both groups were started on a remifentanil infusion at a rate of 0.1-0.4 μg/kg/ min iv.
Cardiopulmonary bypass was performed with using a mem-brane oxygenator, hemodilution and moderate systemic hypo-thermia (28-32°C). Multidose cold crystalloid cardioplegia with potassium (20 mEq/l) and topical saline ice slush were used for myocardial protection during bypass. Patients had median ster-notomy with harvesting of radial artery, saphenous veins and internal thoracic arteries as conduits. Distal anastomoses were performed during continuous aortic cross clamping, followed by proximal vein grafting during partial aortic occlusion. A hemato-crit value of 25-30%, a MAP value of 50-80 mmHg, and CPB flow was maintained between 2-2.5 L/m2.
Before starting to extracorporeal circulation pancuronium 0.05 mg/kg, remifentanil 0.05 μg/kg and pentothal 3 mg/kg were injected into the cardiotomy reservoir in both groups. During extracorporeal circulation, group 1 patients continued to receive sevoflurane in concentrations of 0.5-2%, while group 2 patients continued to receive isoflurane 0.5-2%.
Heart rate (HR), systolic arterial pressure (SAP), mean arte-rial pressure (MAP) and diastolic artearte-rial pressure (DAP) read-ings were recorded just prior to induction (t1), post induction (t2), post intubation (t3), post skin incision (t4), post sternotomy (t5), after the removal of the cross-clamp (t6), at the 10th minute
(t7) and at the 20th minute following completion of the
extracor-poreal circulation (t8), at the 1st hour (t9), at the 6th hour (t10), at
the 12th hour (t11), and at the 24th hour (t12) after admission to
the intensive care unit.
The patients were continuously monitored with regard to inadequate anesthesia depth. The following findings were assumed to indicate in adequate anesthesia: a HR of more than 90 beats/minute lasting for more than 1 minute prior to the CPB, a preoperative baseline SAP value above 150 mmHg prior to CPB, or a SAP of more than 140 mmHg lasting for more than 1 minute prior to or following the CPB, a MAP above 80 mmHg dur-ing CPB, observation of somatic (movements, eye opendur-ing, deglutition) and autonomic (sweating, tear production) respons-es. Whenever in adequate anesthesia depth was observed, the sevoflurane or isoflurane concentrations were increased by 0.5%. Sevoflurane did not exceed 4% and isoflurane did not exceed 2.3%.
Hemodynamically stable, normothermic (body temperature above 36°C) patients without arrhythmias, whose chest tube drainage volume was less than 100 ml/hr, urinary output was greater than 0.5 ml/kg/hr, PaO2 greater than 90 mmHg with an
FiO2 less than 50%, respiratory rate - 10-30/min, pH more than
7.5, and PCO2 less than 55 were extubated.
Laboratory analyses
Arterial blood samples were obtained as follows: baseline sample (before induction of anesthesia), after aortic unclamp-ing, at the 2nd postoperative hour and at the 24th postoperative
hour. Troponin-T, creatine kinase (CK) and CK-MB values were measured in all obtained samples. Samples were centrifuged and frozen at -80°C to be analyzed at laboratory. Photometric determination of the activity of CK (the reference range: 22-240 IU/L), and CK-MB (the reference range:0-25 IU/L) in blood sam-ples that was measured with standard measured by autoanaly-ser (Cobas, Roche, USA). Troponin-T was measured according to manufacturer recommendation by standard immunoassay techniques (Dimension, Newark, USA).
Statistical analysis
Data were processed using the SPSS for Windows version 13.0 program (Chicago, IL, USA). Continuous variables are pre-sented as mean±standard deviation and median (minimum- maximum) values. Intergroup and intra-group comparisons were accomplished using t-test, Chi-sguare test, Mann-Whitney test and two-way analysis of variance. A sample size of 20 patients per group was needed for comparison between two groups (α=0.05, two samples t-test and power of the study of 85%). The statistically significant value was assumed to be p<0.05.
Results
No statistically significant difference was found between Group 1 and Group 2 with respect to demographic characteris-tics, perioperative medications, number of grafts, CPB pump duration and cross-clamping duration (p>0.05; Table 1).
The heart rate data of the cases are shown in Figure 1. Inter-group comparison shows that HR at the 6th postoperative hour is
statistically higher in the sevoflurane group (p<0.05). The data showed no statistically significant difference in the HR between the two groups in the rest of the time intervals (p>0.05).
The HR prior to induction in the sevoflurane group was found to be statistically significantly higher when compared to HR dur-ing the partial pump period, at the 10th minute and 20th minute
following completion of the extracorporeal circulation (p<0.05). In the isoflurane group, the comparison of the heart rates prior to and following induction yielded a statistically significant reduction in HR following induction (p<0.05). The HR values fol-lowing intubation, skin incision, and sternotomy were found to be significantly higher than those following induction (p<0.05).
No statistically significant difference was observed with regard to SBP, DBP and MBP values between the groups (p>0.05).
The troponin-T data are shown in Table 2. The troponin-T val-ues following the removal of the cross-clamp and those at the 24th
postoperative hour were significantly lower in the sevoflurane group when compared to those in the isoflurane group (p<0.05).
Within the sevoflurane group, troponin-T values at the 2nd
and 24th postoperative hours were significantly higher when
compared to the values prior to induction (p<0.05). No statisti-cally significant difference was observed upon comparison of troponin-T values at 2nd and 24th postoperative hours. However,
a decrease in the 24th postoperative hour troponin-T value was
observed with relation to its 2nd postoperative hour value.
Figure 1. Heart rate values of cases. Intergroup comparison shows that HR at the 6th postoperative hour is statistically higher in the sevoflu-rane group (*p=0.025, (ANOVA for repeated measurements)
Prior to induction (t1), post induction (t2), post intubation (t3), postskin incision (t4), poststernotomy (t5), after the removal of the cross-clamp (t6), at the 10th minute (t7) and at the 20th minute following completion
of the extracorporeal circulation (t8), at the 1st hour (t9), at the 6th hour
(t10), at the 12th hour (t11), and at the 24th hour (t12) after admission to
the intensive care unit
HR, breat/min TIME Sevoflurane Isoflurane t1 t2 t3 t4 t5 bypass period t6 t7 t8 * t9 t10 t11 t12 140 120 100 80 60 40 20 0
Variables Sevoflurane Isoflurane p*
(n=20) (n=20) Age, years 59.0±1.5 57.0±1.5 NS Weight, kg 69.0±2.6 72.0±1.8 NS Gender, M/F, n 13/7 15/5 NS Perioperative medication Beta-blockers 19 20 NS Calcium channel blockers 18 17 NS Nitrates 10 10 NS Number of coronary grafts, n 2.5±0.1 2.5±0.1 NS EF, % 55.0±1.6 54.0±1.5 NS Pump duration, min 78.0±2.9 74.0±1.9 NS Cross-clamping duration, min 51.0±2.8 54.0±1.9 NS
Data are expressed as mean±SD values and proportions unpaired t-test and Chi-square test
EF - ejection fraction, F - female, M - male, NS-non-significant (p>0.05)
Within the isoflurane group, troponin-T values at the 2nd and
24th postoperative hours were significantly higher when
com-pared to the values prior to induction (p<0.05). However, there was a statistically significant difference in the troponin-T values at the 24th and 2nd postoperative hours (p<0.05).
The CK data pertaining to the study cases are shown in Table 2. The CK values obtained following after the removal of the cross-clamping, at the 2nd and 24th postoperative hours were
found to be significantly higher in the sevoflurane group than in the isoflurane group (p<0.05).
Within the sevoflurane group, CK values following cross-clamp removal, at the 2nd and 24th postoperative hours were
significantly higher when compared to control values (p<0.05). Within the isoflurane group, CK values prior to induction and following cross-clamp removal were found to be significantly lower when compared to the values at the 2nd and 24th
postop-erative hours (p<0.05).
The CK-MB readings of the cases are shown in Table 2. The CK-MB values at 24th postoperative hour in the sevoflurane
group were found to be significantly lower when compared to the 24th postoperative hour CK-MB values of the isoflurane
group (p<0.05). The CK-MB values at 2nd postoperative hour in
the isoflurane group were found to be higher when compared to the 2nd postoperative hour CK-MB values of the sevoflurane
group, but the increase was not statistically significant (p>0.05). The CK-MB values in the sevoflurane group prior to induc-tion were higher than the values following cross-clamp removal,
but the difference was not statistically significant (p>0.05). The CK-MB values obtained at the 2nd and 24th postoperative hours
were significantly higher than the CK-MB values obtained prior to induction and following cross-clamp removal (p<0.05).
Within the isoflurane group, the CK-MB values obtained at the 2nd and 24th postoperative hours were significantly higher
when compared to the values prior to induction (p<0.05). The second postoperative hour CK-MB values were higher than the values following cross-clamp removal, but the difference was not found to be statistically significant (p>0.05). The CK-MB val-ues obtained at the 24th hour postoperatively were significantly
higher than the values following cross-clamp removal (p<0.05).
Discussion
The results of our study showed that troponin -T and CK-MB values after aortic clamping and at the 24th postoperative hour
were significantly lower in the sevoflurane group when com-pared to those in the isoflurane group.
Transient myocardial dysfunction following CPB is a well described condition. In addition to a sufficient revascularization, elective myocardial protection is needed for the ventricular function to be maintained. There are various factors affecting postoperative myocardial function and extent of myocardial injury (6, 7). Despite the great number of studies conducted, the mechanism of action of volatile anesthetic agents with regard to myocardial injury is not entirely elucidated. However, multiple
Variables Group 1 (n=20) Group 2 (n=20) p* Mean±SD Median (min-max) Mean±SD Median (min-max)
Troponin T, ng/ml
1 0.50±0.45 0.49 (0.445-0.54) 0.476±0.22 0.474 (0.46-0.49) 0.409 2 1.015±0.75 1.10 (0.935-1.185) 1.469±0.150 1.397 (1.29-1.645) <0.001 3 6.112±0.524 6.1 (5-7) 4.11±0.53 4.1 (3.2-5.1) <0.001
4 5.340±0.654 5.20(4.37-5.96) 8.71±1.03 8.8 (7.2-10.8) <0.001 Creatine kinase, IU/L
1 89.25±3.44 99 (87-96) 97.15±9.99 98 (79-106) 0.002 2 216.10±6.22 217 (205-227) 143.2±11.64 144 (127-171) <0.001 3 449.1±3.1 448 (446-452) 252.5±4.8 254.5 (247.5-262.0) <0.001 4 768.05±5.56 769 (760-780) 465.85±8.17 466.5 (450.0-486.0) <0.001 Creatine kinase MB, IU/L
1 26.75±2.41 26.8 (23.0-31) 27.85±3.39 26.5 (23.0-33.0) 0.244 2 48.15±2.28 48.2 (45.0-53.0) 52.35±2.70 53 (48-57) <0.001 3 113.35±3.12 113 (109-118) 87.30±3.57 87 (80-95) <0.001 4 104.75±3.46 103.8 (99.0-110.0) 155.60±4.88 156 (146-163) <0.001
Data are expressed as mean±SD values and median(minimum-maximum) values *Unpaired t-test and Mann-Whitney U test
1-before induction of anesthesia, 2-after aortic clamping, 3-at the 2nd postoperative hour, 4-at the 24th postoperative hour
mechanisms have been reported to participate in anesthetic myocardial protection (3, 8-10). Volatile anesthetic agents, when administered prior to and following ischemia, have been report-ed to improve cardiac function and decrease the frequency of revascularization rhythm disturbances (11, 12). This feature has been linked to anesthetic preconditioning effect; however, vola-tile anesthetics have been reported to provide protection even when administered during the revascularization period only (4).
De Hert et al. (4) administered 4 different anesthesia proto-cols to the 200 patients scheduled to be subjected to CPB. The first group received intravenous propofol anesthesia, the sec-ond group was given sevoflurane until CBP, in the third group sevoflurane was initiated after the coronary anastomoses were completed, and the forth group was kept on sevoflurane until the surgery was completed. The results showed that the cardiac protective effect in the group on continuous sevoflurane admin-istration during the surgery was clinically significant. This group had lower troponin-I levels and better cardiac function when compared with the group on intravenous propofol anesthesia. In the groups where sevoflurane was administered only prior to CBP and only after completion of the coronary anastomosis an earlier recovery of the postoperative stroke volume was noticed, but postoperative Troponin-I levels failed to demonstrate a sig-nificant difference when compared to the intravenous anesthe-sia group (4). Ebert et al. (13) compared sevoflurane and isoflu-rane in CPB cases basing on the HR increase produced by the surgery, and found the HR increase with sevoflurane to be less than that with isoflurane. It was observed that the HR of patients with coronary artery disease patients undergoing cardiac or noncardiac surgery was more stable with sevoflurane. Similarly, we found no significant difference between the two groups of our study with respect to increase in HR as a response to surgi-cal stimuli. In the sevoflurane group, we did not found any statis-tically significant difference in the HR prior to induction when compared to the readings following induction, following skin incision, following sternotomy and during follow-up in the inten-sive care unit. On the other hand, the HR during the aortic side-clamp period, at the 10th and 20th minutes following pump
detachment were higher when compared to the readings prior to induction. During the hypothermia period, a reduction in the metabolism and clearance rates of anesthetic agents is expect-ed secondary to hemodilution and nonpulsatile perfusion (14). Immediately following the CPB ending, the heart rate of the surgically injured stunned myocardium increases secondary to increased clearance and increased metabolic rate. This explains the increase in the HR upon completion of the bypass surgery.
Searle et al. (15) used isoflurane and sevoflurane as a vola-tile anesthetic agents in patients scheduled for elective CPB surgery. No difference was noticed in the cardiovascular effects of either agent. However, they had not investigated the myocar-dial protection effects of these agents. There was a similar decrease in SBP, HR and cardiac index in both groups following anesthesia induction. Hemodynamic data remained stable
fol-lowing endotracheal intubation, skin incision and sternotomy. The authors’ comment on their study results was that both agents seemed to be useful in providing for the hemodynamic control in low-risk CPB surgical patients. The incidence of intra-operative myocardial ischemia and postintra-operative morbidity and mortality incidences were found to be similar in both groups.
Bennett et al. (16) in their study which included 60 patients, maintained anesthesia with either sevoflurane or isoflurane at the beginning of surgery and evaluated myocardial injury using transesophageal echocardiography (TEE) and electrocardiogra-phy (ECG). Though recovery properties were found to be similar with equal doses of sevoflurane or isoflurane, sevoflurane was stated to be more useful.
Malagon et al. (17) compared three different anesthesia techniques with regard to their effects on myocardial protection in 90 pediatric patients scheduled for CPB surgery. Patients received midazolam, propofol and sevoflurane, and troponin-T values within the first 24 hours following surgery were com-pared. In all three groups troponin-T levels were found to be significantly high. As a result, based on troponin-T values, the myocardial protection in all of the three groups was found to be equal. They found that contrary to adult coronary bypass sur-gery, sevoflurane did not reduce troponin-T levels significantly, when compared to propofol.
Hemmerling et al. (18) compared the cardioprotective effects of sevoflurane and isoflurane in off-pump cardiac bypass sur-gery. Unlike our study, it has been shown that sevoflurane and isoflurane provide the same ischemic cardioprotective effects.
Cardiac troponin-T is a protein found in the heart muscle and is specific for myocardial tissue. This protein is quite sensitive for myocardial necrosis (19). It is not encountered in the blood of healthy subjects. Jaffe et al. (20) defined cardiac troponin as more useful and more sensitive markers of myocardial injury when compared to CK-MB.
Troponin-T level was one of the parameters we used to evaluate the extent of myocardial injury in our study. We found that its values were higher following cross-clamp removal (median value sevoflurane: 1.01, isoflurane: 1.46), at the 2nd
(sevoflurane: 6.11, isoflurane: 4.11) and 24th postoperative hours
(sevoflurane: 5.34, isoflurane: 8.71), when compared to values prior to induction (sevoflurane: 0.5, isoflurane: 0.48). However, the increase following the 2nd postoperative hour was observed
to be less in the isoflurane group as compared to the sevoflu-rane group. We also observed that creatine kinase values, one of our other parameters, were higher when compared to its pre-induction levels. The increase in CK in the sevoflurane group was more than that observed in the isoflurane group, as indi-cated by the values following cross-clamp removal (median value sevoflurane: 216, isoflurane: 138) at the 2nd (sevoflurane:
449 isoflurane: 449 isoflurane: 252) and 24th postoperative hours
sevoflurane: 104, isoflurane: 155) postoperative hour levels, we found CK-MB values to be significantly lower in the sevoflurane group than in the isoflurane group. None of the cases in our study suffered perioperative myocardial infarction, and all patients completed the study. Postoperative complications were found to be similar for both groups of the study.
Study limitations
There are limitations to our study. Firstly, histopathological species may support the blood data. Secondly, long-term follow-up of patients for cardiac function may have been included in our study.
Conclusion
Based on our results, we conclude that by providing suffi-cient anesthesia level and hemodynamic stability, both of the inhalational anesthetics, sevoflurane and isoflurane. In our opin-ion, sevoflurane provides a better myocardial protection than isoflurane, as may be inferred by the lower levels of the myocar-dial injury markers troponin-T and CK-MB observed with sevo-flurane. Further studies are necessary to address the potential influence of choices of anesthetic regimens on long- term car-diac function after coronary surgery.
Conflict of interest: None declared.
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